Effect of Transporter Genotype on the Rate of Caffeine Absorption

Caffeine is the most widely used psychoactive drug in the world, with the majority of the world’s population consuming it on a daily basis. Individuals respond very differently to caffeine, with both environmental factors and genetic variation of proteins involved in metabolism, mode of action, and absorption believed to modulate caffeine’s effects. For example, a single nucleotide polymorphism (rs762551) of the gene for the liver enzyme CYP1A2 has been reported to influence caffeine outcomes, with “slow” metabolizers having reduced benefits of caffeine during exercise and increased risk of heart attack. Our working hypothesis is that single nucleotide polymorphisms in the nucleoside transporter protein ENT1, encoded by SLC29A1, may play a role in caffeine absorption, a topic that has widespread medical significance. In this study, human subjects were genotyped at the SLC29A1 locus for SNP rs760370, previously suggested to modulate the efficacy of nucleoside analogue therapy. Subjects were also phenotyped via ELISA to determine how fast they actually absorb caffeine. We have observed significant variability in tmax (time to maximum concentration) among our subjects and are assessing a potential relationship between tmaxand a subject’s genotype to determine whether some genotypes correlate with faster rates of caffeine absorption. Overall, this work may contribute to a better understanding of the variable effects of caffeine consumption, as well as inform the timing of caffeine dosing for those seeking to enhance alertness and/or performance.